Hepatitis C Virus (HCV)
Conditions
Keywords
Chronic Hepatitis C Virus (HCV), Genotype 1 - 6, Metavir System Fibrosis Score, Glecaprevir, Pibrentasvir, Treatment naïve, Cirrhosis, Compensated cirrhosis
Brief summary
This was a Phase 3, open-label, multicenter study to evaluate the efficacy and safety of glecaprevir (GLE)/pibrentasvir (PIB) for an 8 or 12-week treatment duration in adults in Brazil with chronic hepatitis C virus (HCV) genotype (GT) 1 to GT6 infection, without cirrhosis or with compensated cirrhosis, who were HCV treatment-naïve.
Detailed description
This was a Phase 3, open-label, multicenter study to evaluate the efficacy and safety of GLE/PIB for an 8- or 12-week treatment duration in adults in Brazil with chronic HCV GT1 to GT6 infection, without cirrhosis or with compensated cirrhosis with a METAVIR System Fibrosis Score of F2 to F3 (without cirrhosis) or F4 (with compensated cirrhosis) or equivalent, who were HCV treatment-naïve.
Interventions
Film-coated tablet
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant had positive plasma hepatitis C virus (HCV) antibody and HCV ribonucleic acid (RNA) viral load greater than or equal to 1000 IU/mL at Screening Visit. * Participant must have been documented as without cirrhosis with METAVIR equivalent fibrosis stage of F2 to F3 or with compensated cirrhosis (F4) based on results of a liver biopsy, or FibroScan, or FibroTest score. * Participants who were known to be HCV/Human Immunodeficiency Virus (HIV) co-infected may have been enrolled if they had a positive test result for anti-HIV antibody at Screening and were: naïve to treatment with any antiretroviral therapy (ART), or on a stable, qualifying HIV ART regimen for at least 8 weeks prior to Baseline. * Participants with compensated cirrhosis only: Absence of hepatocellular carcinoma (HCC) within 3 months prior to Screening or a negative ultrasound at Screening.
Exclusion criteria
* Current hepatitis B virus (HBV) infection on screening tests. * Any current or past clinical evidence of Child-Pugh B or C classification (score of \> 6) or clinical history of liver decompensation including ascites on physical exam, including hepatic encephalopathy or variceal bleeding. * Receipt of any investigational or commercially available anti-HCV agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after last dose of study drug (week 20 or 24 depending on treatment regimen) | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment HCV Virologic Failure | 8 or 12 weeks (depending on treatment regimen) | On-treatment HCV virologic failure was defined as one of the following: * Confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ 100 IU/mL after HCV RNA \< 15 IU/mL at any time point during treatment; or * Confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir) during study drug treatment; or * HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment HCV Virologic Relapse | From the end of treatment (8 or 12 weeks depending on treatment regimen) through 12 weeks after the last dose of study drug | Post-treatment HCV virologic relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA levels \< 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed. |
Countries
Brazil
Participant flow
Pre-assignment details
A total of 100 participants were enrolled and received ≥ 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks Arm A: Hepatitis C virus (HCV) genotype (GT) 1 to GT6 participants without cirrhosis (fibrosis stage F2 to F3) received glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks. | 75 |
| Arm B: GLE/PIB for 12 Weeks Arm B: HCV GT1 to GT6 participants with compensated cirrhosis (F4) received GLE/PIB 300 mg/120 mg once daily (QD) for 12 weeks. | 25 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Arm B: GLE/PIB for 12 Weeks | Total | Arm A: Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks |
|---|---|---|---|
| Age, Continuous | 56.44 years STANDARD_DEVIATION 9.62 | 54.51 years STANDARD_DEVIATION 10.9 | 53.87 years STANDARD_DEVIATION 11.28 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 4 participants | 26 participants | 22 participants |
| Race/Ethnicity, Customized Multi-race | 3 participants | 9 participants | 6 participants |
| Race/Ethnicity, Customized White | 17 participants | 63 participants | 46 participants |
| Sex: Female, Male Female | 5 Participants | 36 Participants | 31 Participants |
| Sex: Female, Male Male | 20 Participants | 64 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 30 / 100 |
| serious Total, serious adverse events | 4 / 100 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after last dose of study drug (week 20 or 24 depending on treatment regimen)
Population: All enrolled participants who received at least one dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders. Data are reported for the overall study population according to the prespecified analysis plan for this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 98.0 percentage of participants |
Secondary
Percentage of Participants With On-treatment HCV Virologic Failure
On-treatment HCV virologic failure was defined as one of the following: * Confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ 100 IU/mL after HCV RNA \< 15 IU/mL at any time point during treatment; or * Confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir) during study drug treatment; or * HCV RNA ≥ 15 IU/mL at the end of treatment with at least 6 weeks of treatment.
Time frame: 8 or 12 weeks (depending on treatment regimen)
Population: All enrolled participants who received at least 1 dose of study drug. Data are reported for the overall study population according to the prespecified analysis plan for this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Participants With On-treatment HCV Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment HCV Virologic Relapse
Post-treatment HCV virologic relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA levels \< 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.
Time frame: From the end of treatment (8 or 12 weeks depending on treatment regimen) through 12 weeks after the last dose of study drug
Population: All enrolled participants who received at least 1 dose of study drug and who completed treatment, had HCV RNA \< 15 IU/mL at final treatment visit, and had at least one post-treatment HCV RNA value. Data are reported for the overall study population according to the prespecified analysis plan for this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Participants With Post-treatment HCV Virologic Relapse | 1.0 percentage of participants |